The long term objectives of the program are to determine the physiologic, biochemical, and molecular mechanisms responsible for the leaner body mass observed in the Spot 14 null mouse. The Spot 14 gene is rapidly upregulated by triiodothyronine (T3) and carbohydrate feeding. Subsequent studies have suggested that the Spot 14 protein is involved in de novo lipogenesis. De novo lipogenesis is a process in which the cell makes fatty acids from carbohydrate. In order to gain insight into the function of the Spot 14 protein we deleted the gene in vivo and created a Spot 14 null mouse. The Spot 14 pups were found to weigh less than there wild type counterparts. We believe that this weight difference can be attributed to defective lipogenesis in the mammary gland of the Spot 14 null mice. The studies outlined in this proposal will further our understanding of the regulation of mammary gland lipogenesis. Since alterations in lipogenesis may lead to the phenotypically observed leaner Spot 14 null mouse, these studies have major implications for the pathophysiologic mechanisms influencing obesity.